The PITX3 gene encodes a homeobox transcription factor, which is a member of the PITX subfamily of paired-like homeobox proteins. In the mammalian brain, PITX3 is expressed in midbrain dopaminergic neurons and is involved in molecular development of dopaminergic neurons in the substantia nigra and for postnatal survival of a subset of dopaminergic neurons in the ventral tegmental area (Smidt et al. 2004; Korotkova et al. 2005; Castillo-Carranza et al. 2008). A double mutation in the mouse PITX3 gene leads to abnormal lens and ocular development in aphakia mice (Rieger et al. 2001). The midbrain/dopaminergic neurons are absent in ak/ak mouse embryos, starting at day 12.5. Midbrain dopaminergic pathways are implicated in control of many brain functions, including those involved in psychiatric and neurological disorders, including Parkinson's disease (PD).
Castillo-Carranza et al. (2008) disclose a 4.8 kb mouse PITX3 promoter construct and analysis of its expression in a human neuroblastoma cell line.
Coulon et al. (2007) disclose a number of mouse PITX3 promoter construct and analysis of expression from these promoters in mouse embryonic development, particularly muscle-specific expression.
There exists a significant need for promoter elements which are capable of driving expression in specific cell types and/or in specific regions of the brain. Identification of minimal elements required for adequate expression and specificity will allow ease of use in expression constructs.